Abstract:
Objective To investigate the expression of Grb2 binding protein-2(Gab2) in gastric cancers and its significance and mechanism in the invasiveness and metastasis of gastric cancer.
Methods Immunohistochemical method was used to detect the expression of Gab2, E-cadherin, N-cadherin and MMP-9 in gastric cancer tissues. The relationship between Gab2 expression and lymphatic metastasis was analysed. SiRNA plasmid targeting Gab2 and empty vector plasmid were transfected into SGC7901 cells and named siGab2/SGC7901 and NC/SGC7901 cells respectively. RT-PCR method was applied to analyze mRNA expression of Gab2 in siGab2/SGC7901 and NC/SGC7901 cells. In vitro matrigel invasion assay was used to detect the invasiveness of siGab2/SGC7901 and SGC7901 cells. Western blot was applied to analyze protein expression.
Results Gab2 expression in gastric cancer tissues was related with lymphatic metastasis significantly(P=0.002), E-cadherin expression level negatively (r=-0.693, P=0.000), and N-cadherin and MMP-9 levels positively (r=0.407, P=0.021; r=0.335, P=0.017). After microRNA interference, the mRNA and protein expressions of Gab2 in siGab2/SGC7901 cells were decreased obviously, moreover, the quantity of gastric cancer cells which invaded and penetrated matrigel membrane was decreased. Western blot showed that the expressions of N-cadherin and MMP-9 were decreased and E-cadherin expression was increased in siGab2/SGC7901 cells.
Conclusion Gab2 plays a key role in the invasiveness and metastasis of gastric cancer by regulating EMT.
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